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Outcome After Systemic Thrombolysis Is Predicted by Age and Stroke Neurology International 2012; volume 4:e9 Outcome after systemic rological deficit at stroke admission, and a proximal MCA occlusion. Half of the surviving Correspondence: Rüdiger J. Seitz, Department of thrombolysis is predicted by patients improved to no or minimal impair- Neurology, University Hospital Düsseldorf age and stroke severity: an ment. Moorenstrasse 5, 40225 Düsseldorf, Germany. open label experience with Tel. +49.211.8118974 - Fax: +49.211.8118485. recombinant tissue E-mail: [email protected] plasminogen activator and Introduction Key words: brain infarct, stroke, thrombolysis, tirofiban tirofiban, impairment. Systemic thrombolysis with the recombi- Funding: the study was supported by the Rüdiger J. Seitz,1,2,3 Judith Sukiennik,1 nant tissue plasminogen activator (rtPA) is the Competence Net Stroke of the BMBF. Mario Siebler1,4 only approved treatment of acute ischemic stroke. It aims at rapid recanalization of the Conflict of interests: the authors report no poten- 1Department of Neurology, University occluded cerebral artery affording neurological tial conflict of interests. Hospital Düsseldorf, 2Biomedical recovery.1 In recent years it was shown that Research Centre, Heinrich-Heine- early recanalization results in better neurolog- Received for publication: 28 September 2011. University Düsseldorf, Germany; ical outcome and less lesion growth than lack- Revision received: 11 June 2012. 3 Accepted for publication: 30 July 2012. Florey Neuroscience Institutes, ing recanalization.2-4 However, the severity of Melbourne, Australia; 4Department the ischemic attack prior to thrombolytic treat- This work is licensed under a Creative Commons of Neurology, Mediclin Fachklinik Rhein ment and a poor status of arterial collaterals Attribution NonCommercial 3.0 License (CC BY- Ruhr, Essen, Germany have been described to predict a poor recov- NC 3.0). ery.5,6 On average, thrombolysis has been found to enhance the proportion of patients ©Copyright R.J. Seitz et al., 2012 Licensee PAGEPress, Italy with a favorable outcome after ischemic stroke Neurology International 2012; 4:e9 Abstract and to downsize the proportion of patients with doi:10.4081/ni.2012.e9 severe neurological deficits.7-9 In fact, a large Stroke patients can recover upon intra- recent meta-analysis of different thrombolysis venous thrombolysis but remain impaired in studies revealed that the application of through 2007. We investigated four questions: lacking recanalization. We sought to investi- alteplase rendered some 42 percent of patients i) what is the proportion of patients who bene- gate the clinical effect of systemic thrombolysis with an excellent outcome [modified Rankin fit from this treatment? ii) what is the propor- with an intravenous bolus of 20 mg recombi- Scale (mRS) of 0 and 1] on day 90 as compared tion of patients who do not benefit from this nant tissue plasminogen activator (rtPA) and with 30 percent of patients receiving placebo.10 treatment? iii) what is the proportion of an infusion of body-weight adjusted tirofiban Prompted by the results of platelet receptor patients who expire after this stroke treat- for 48 hours in acute stroke. This prospective, inhibition in the management of patients with ment? iv) what are predictors for poor or good open label study, included 192 patients (68±13 acute myocardial ischemia we have introduced recovery? years, 50% males) treated between 1 January a regime for systemic thrombolysis composed 2005 and 31 December 2007. The neurological of an intravenous bolus of low dose rtPA in deficit was assessed with the National combination with a subsequent infusion of the Institutes of Health stroke scale (NIHSS). nonpeptide GPIIb/IIIa platelet receptor antago- Materials and Methods Follow-up was performed using a telephone nist tirofiban.11,12 The rational for a low dose of interview of modified Rankin Scale (mRS) and rtPA was to avoid intra- and extracranial hem- Subjects Barthel index. The site of cerebral artery occlu- orrhage, since symptomatic and fatal hemor- All patients who were treated with systemic sion was determined by computed tomography rhages are a severe complication of a high thrombolysis on the Stroke Unit of our institu- or magnetic resonance angiography. Data were dose of rtPA.13 Further, GPIIb/IIIa receptor tion between 1 January 2005 and 31 December analyzed by descriptive statistics and multiple antagonists selectively inhibit the platelet regression analyses. Eighty-one percent of the integrin IIbIII fibrinogen receptor and there- 2007 were included. Criteria for inclusion into patients had an infarct in the middle cerebral by inhibit platelet aggregation.14,15 Since rtPA this study were: artery (MCA) territory and were severely affect- is known to induce a hypercoagulation follow- - an acute ischemic brain infarct, ed with a median NIHSS of 10. During treat- ing thrombolysis,16 tirofiban was expected to - documentation of a causal cerebral artery ment on the Stroke Unit the patients improved antagonize the hypercoagulation following occlusion before thrombolysis using com- (P<0.0001) except for patients who deceased rtPA administration and thereby help to main- puted tomographic angiography (CTA) or due to malignant infarction (n=10) or cerebral tain the cerebral blood vessels patent after magnetic resonance angiography (MRA), haemorrhage (n=6); 18 percent deceased with- thrombolysis. Likewise, it might help to disag- - systemic thrombolysis with rtPA and in 100 days which was predicted by older age gregate secondary thrombi resulting from the tirofiban, (76 + 10 years, P<0.05) and more severe affec- large thrombus in the initially occluded cere- - clinical evaluation on admission and at dis- tion on admission (P<0.0001). Also, these bral artery. We have shown previously that the charge from the Stroke Unit using the patients more frequently had atrial fibrillation combined use of low dose rtPA and tirofiban is stroke scale of the National Institutes of (P<0.03) than the surviving patients. The sur- safe and effective.12,17 Thus, we used this Health (NIHSS), the mRS and Barthel index viving patients had more frequently distal MCA treatment as first line regime. (BI),18-21 occlusions and improved further (P<0.0001). In this prospective mono-center, non-ran- - follow-up telephone questionnaire of the BI At follow-up 48% of the patients had a mRS of 0 domized study we analyzed the clinical data of and mRS, which was performed after at least and 1. Similarly to intravenous thrombolysis the consecutive patients treated with a low 130 days (median 487 days, range 131-1056 with body-weight adjusted rtPA, poor prognosis bolus of rtPA and a subsequent infusion of days). was predicted by higher age, more severe neu- tirofiban in our hospital in the years 2005 Patients were subjected either to computed [Neurology International 2012; 4:e9] [page 35] Article tomography including CTA or multiparametric 0.001). Twenty-three patients died with 6 magnetic resonance imaging including a MRA patients due to an intracranial haemorrhage Discussion depending on availability prior to thrombolysis. (3.1%) and 10 patients suffering malignant Thrombolysis was performed in each patient brain infarction. After discharge eleven further This study revealed that the combined use with an intravenous bolus of 20 mg rtPA with- patients deceased such that 34 patients (18%) of an intravenous bolus of low dose rtPA and a in 3 h after stroke onset followed immediately deceased within 100 days after stroke (Figure subsequent body-weight adjusted infusion of by an intravenous infusion of tirofiban.12,17 2). Death was predicted by older age (76±10 tirofiban had an optimal outcome (mRS of 0 Tirofiban was given in a body-weight adjusted years, P<0.05) and a more severe affection and 1) at follow-up in about 48 percent of our dosage starting with a bolus of 0.4 mg/ kg body (mRS 5, P<0.0001). Also, the patients more fre- patients. In comparison to the large clinical tri- weight/min for 30 min followed by continuous quently had atrial fibrillation (P<0.03) than the als of systemic application of rtPA this was infusion of 0.1 mg/ kg body weight/min for 48 h. surviving patients. But none of the other vascu- clearly better than in the placebo group and In addition, patients were treated according to lar risk factors was predicting or different similar to the thrombolysis group.10 Note, that their individual requirements. The treatment between the deceased or surviving patients the patients in this study had a median NIHSS procedure and the study were approved by the (Table 1). The surviving patients improved fur- at treatment onset of 10 being as severely Ethics Committee of the Heinrich-Heine- ther (P<0.0001) leaving 48% of study cohort affected as the patients in the ECASS 3 study.1 University Düsseldorf, Germany. The patients with a mRS of 0 and 1 at follow-up, while 18 % Importantly, the patients who benefitted from gave informed consent. of the patients were still severely affected hav- our treatment regime were younger and less ing a mRS of 4 or 5 (Figure 3). severely affected at stroke onset than those Statistical analysis Statistical analysis was done using SPSS 10.1 for Windows (release 2005). Group comparisons were done using the two-tailed t-test. Evaluation Table 1. Characteristics of the 192 patients. of the neurological deficit and the impairment was assessed with the non-parametric Mann- Age (years ± SD) 70±13 Whitney test. Group comparison of the abnor- Male/Female (n) 95/97 malities in the
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